This invention relates to antacids containing zeolitic alkali aluminosilicates of A, X, Y, or P type molecular sieves or mixtures thereof in their sodium and/or potassium forms. The invention also relates to the use of zeolitic alkali aluminosilicates of A, X, Y, or P type molecular sieves or mixtures thereof in their sodium and/or potassium forms for the production of antacids and the use thereof in the treatment of hyperacidity and related conditions.
Antacids are medicaments which neutralize excess stomach acid. They are indicated for stomach disorders caused by hyperacidity and for hyperacidity-related Ulcus ventriculi or Ulcus duodemi. Further indications include heartburn acidic eructation, feeling of fullness, hyperacidity, reflux oesophagitis, heartburn in pregnancy, stomach complaints after alcohol and nicotine abuse and after errors in diet, hiatus hernia, colitis, treatment and prophylaxis of the "stress ulcer", Gastrophatia neurogenica, medication-related hyperacidity and also "upset" stomach.
Accordingly, antacids are not only particularly important in the treatment of ulcers, they are also the most widely prescribed medicaments, even though in most instances they can be obtained without a prescription. The state of the art in this field is exemplified by the following publications: W. Leetsch, Deutsche Apothekerzeituny 114, 1307 (1974) "Antacida und das Problem ihrer Wirksamkeitsbeurteilung (Antacids and the Problems of Assessing their Effectiveness)"; H. Ruppin, Med. Klin. 70, 1237 (1975) "Theoretische und Klinische Aspekte der Antacidatherapie" (Theoretical and Clinical Aspects of Antacid Therapy) ; K. H. Holtermuller, E. Bohlen, M. Castro and H. J. Weis, Med. Klin. 72, 1229 (1977) "Uberlegungen zur Therapie mit Antacida (Reflections on Therapy with Antacids)"; H. Brunner, E. Penner and G. Grabner, Ost. Arztetg. 32/1, 27 (1977) "Sind Antacida Plazebos? (Are Antacids Placebos?)"; R. Glluer, Schweiz. med. Wschr. 107, 807 (1977) "Pufferkapazitat und Kosten der flussigen Antazida 1977 (Buffer Capacity and Costs of Liquid Antacids 1977)"; S. B. Siskin, University of Michigan, Medical Center Journal 40, 93 (1974) "Over the Counter Drug Review: Antacid Products"; J. Schnekenburger, Arzneim.-Forsch. (Drug Res.) 24, 142 and 275 (1974) "In-vitro-Untersuchungen an Antazida (in vitro Studies of Antacids)"; J. Schnekenburger, Loc.cit. 31 (II), 1286 (1981) "In-vitro-Untersuchungen an Antacida (In-vitro Studies of Antacids)".
This prior art contains information on the chemical action of antacids, lists advantages and disadvantages of market preparations and describes galenic forms thereof, evaluation criteria, cost/profit ratios and methods for the in-vitro testing of antacids.
The most common substances active as antacids are sodium bicarbonate, calcium carbonate, magnesium carbonate, aluminum hydroxide, aluminum phosphate, magnesium trisilicate, aluminum magnesium trisilicate hydrate, and sodium aluminum silicate. Most, if not all, of these active substances have undesirable side effects which are of importance, particularly when the substances in question are taken regularly. Sodium bicarbonate reacts very quickly with the stomach acid to form carbon dioxide (troublesome gas production); excess sodium bicarbonate is absorbed (particularly troublesome in the case of hypertonics) and displaces the acid-base equilibrium to the alkaline side (causing alkalosis, milk alkali syndrome). Alkaline reaction in the stomach brought about by excess sodium bicarbonate gives rise to compensatory acid production, commonly referred to as "acid rebound".
These effects also occur when calcium carbonate is taken. In addition, during the actual neutralization phase, calcium carbonate produces an increase in the release of gastrin which in turn stimulates the secretion of acid. Considerable quantities of calcium are absorbed, and especially in the event of repeated application, can lead to renal calcinosis.
Magnesium salts have a laxative effect. Also, due to the danger of accumulation, they are contraindicated in cases of renal malfunction.
When taken over a prolonged period (2 to 3 weeks), aluminum salts formed as reaction products of aluminum-containing antacids cause phosphate depletion. In addition, emptying of the stomach is delayed by inhibition of the contraction of the smooth musculature and slight blockage can occur.
Silicates used as antacids produce the same side effects as magnesium and aluminum salts. In general, however, treatment with these antacids is regarded as safe. The antacid silicates bind acid while leaving a certain residual acidity.
German Patent Application DE No. 20 29 265 describes an antacid mixture which contains sodium aluminum silicate and milk powder. However, this sodium aluminum silicate is not a zeolitic sodium aluminosilicate, as can be seen from the following discussion.
Although the term "sodium aluminum silicate" is a generic term for all products of the type xNa.sub.2 O.Y Al.sub.2 O.sub.3.z SiO.sub.2 for x, y, Z.noteq.0, the term does exclude compounds of the type in which the aluminum is attached to the silicate tetrahedrons in the form of an AlO.sub.4 tetrahedron, i.e. through oxygen bridges. This is apparent from standard text books on inorganic chemistry, for example those by Remy 12th Edition, Vol. I, page 615, 1965) or Holleman-Wiberg (81st - 90th Edition, pages 553-554, 1976) in which the latter, tetrahedron-attached compounds are distinctly referred to as "sodium aluminosilicates". Gmelin (XI*, XII*) Volume "Aluminum Part B" also distinguishes between "sodium aluminum silicates" and "zeolites".
Accordingly, German Patent Application DE No. 20 29 265 excludes zeolitic antacids. This is also confirmed by the following statement in the descriptive part of this Application (page 3/4): "Irrespective of the route selected for oral ingestion, aluminum sodium silicate has an extremely disagreeable taste and is very unpleasant to take". A "disagreeable" taste is a well known characteristic of sodium aluminum silicates of the type defined above containing Al.sup.3+ -cations which are not tetrahedrally surrounded by oxygen. Zeolitic sodium alumosilicates on the other hand have a neutral taste which cannot be characterized as "disagreeable".
East German Pat. No. 103,429 describes a process for the production of a sodium alumosilicate gel which corresponds to the composition Na.sub.2 O . Al.sub.2 O.sub.3 . 2SiO.sub.2 . aq and which has antacid properties. On page 2, left-hand column, this East German Patent describes highly crystalline molecular sieves (zeolites) as prior art and states that, although these zeolites show certain acid-binding properties, these antacid properties are not sufficient to enable the zeolites in question to be pharmaceutically used as antacids. Accordingly, compounds other than zeolites, namely sodium aluminum silicate gels, are produced in East German Pat. No. 103,429 where they are said to be suitable for use as antacids. This prior art teaches those skilled in the art not to use zeolitic, and hence crystalline, sodium aluminum silicates as antacids. During the development of the present invention tests were conducted for comparison with the teachings of the East German Pat. No. 103,429 and are discussed in detail hereinafter.